Abstract
Enterococcus faecalis is a commensal opportunistic pathogen found in the intestine, mouth, and vaginal tract of humans. As an invasive pathogen in the oral cavity, E. faecalis is one of the leading causes of periapical endodontic lesions. However, due to the strong biofilm-forming capacity and tolerance of E. faecalis to conventional antibiotics and treatments, limited therapeutic options are available. In the present study, we investigated the activity of ClyR, a chimeric lysin with extended streptococcal lytic spectrum, against planktonic and sessile E. faecalis cells in vitro and in an ex vivo dental model. Our results showed that ClyR has robust and rapid lytic activity against multiple E. faecalis strains, killing >90% planktonic cells within 1 min at a concentration of 50 μg/mL. The biochemical experiments combined with microscopy analysis revealed that ClyR degrades E. faecalis biofilm with high efficacy in a dose-dependent manner, reducing the survival rate to <40% within biofilms after treatment with 50 μg/mL ClyR for 1 h. In the ex vivo dental model, ClyR showed a significant biofilm removal efficacy, killing >90% viable bacteria within biofilms at a low dose of 50 μg/mL, which is much better than ampicillin and similar to calcium hydroxide, the extensively used routine intracanal medicament in the treatment of endodontics and dental traumatology. The robust activity of ClyR against both planktonic and sessile E. faecalis suggests the potential of ClyR in treating endodontic infections caused by E. faecalis.
Highlights
Enterococcus faecalis, an opportunistic Gram-positive pathogen, is a member of the normal microorganisms of the oral cavity, intestines, and vaginal tract of human beings and animals [1].As a common community of oral microbiota, E. faecalis has found to be involved in the microflora of the root canal and the periodontal pocket that do not respond well to conventional root canal therapy [2]
Due to their robust cell lysis capacity, lysins have been found capable of degrading bacterial biofilms through a layer-by-layer model, for instance, PlyC is highly active against Streptococcus pyogenes biofilm [15], several staphylococcal lysins have reported to be active against Staphylococcus aureus biofilm in vitro and in skin infection models, lysin LySMP is capable of removing Streptococcus suis biofilm [25], pneumococcal lysins Cpl-1 and Cpl-7 are efficient against Streptococcus pneumoniae biofilm [26], and ClyR has reported to be the first lysin that is active against Streptococcus mutans biofilm [27]
Few lysins with significant bactericidal activity against E. faecalis have been developed to date, including the chimeric lysin ClyR that comprises the CHAP domain of PlyC lysin and the cell-wall binding domain of PlySs2 lysin and shows extended streptococcal lytic spectrum [28], the natural lysin LysEF-P10 [29], and the chimeric lysin EC300 [30]
Summary
Enterococcus faecalis, an opportunistic Gram-positive pathogen, is a member of the normal microorganisms of the oral cavity, intestines, and vaginal tract of human beings and animals [1].As a common community of oral microbiota, E. faecalis has found to be involved in the microflora of the root canal and the periodontal pocket that do not respond well to conventional root canal therapy [2]. Lysins encoded by bacteriophages can cause a time-clocked cell lysis from within, and can result in rapid cell wall degradation against a susceptible Gram-positive bacterium when added exogenously [16,17] Due to their robust cell lysis capacity, lysins have been found capable of degrading bacterial biofilms through a layer-by-layer model, for instance, PlyC is highly active against Streptococcus pyogenes biofilm [15], several staphylococcal lysins (such as CF-301 [18], ClyH [19], ClyF [20], phi endolysin [21], SAL-2 [22], Ply187AN-KSH3b [23], P128 [24] and so on) have reported to be active against Staphylococcus aureus biofilm in vitro and in skin infection models, lysin LySMP is capable of removing Streptococcus suis biofilm [25], pneumococcal lysins Cpl-1 and Cpl-7 are efficient against Streptococcus pneumoniae biofilm [26], and ClyR has reported to be the first lysin that is active against Streptococcus mutans biofilm [27]. As far as we know, no study has been done on using lysins to treat biofilms of E. faecalis in dental models
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